Ecological Exposure Research Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Cincinnati, Ohio, USA.
Environ Toxicol Chem. 2013 Aug;32(8):1828-34. doi: 10.1002/etc.2254. Epub 2013 Jun 21.
Gamma-aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic-pituitary-gonadal axis, leading to impaired fish reproduction. The present study used a 21-d fathead minnow (Pimephales promelas) reproduction assay to investigate the reproductive toxicity of fipronil (FIP), a broad-spectrum phenylpyrazole insecticide that acts as a noncompetitive blocker of GABA receptor-gated chloride channels. Continuous exposure up to 5 µg FIP/L had no significant effect on most of the endpoints measured, including fecundity, secondary sexual characteristics, plasma steroid and vitellogenin concentrations, ex vivo steroid production, and targeted gene expression in gonads or brain. The gonad mass, gonadosomatic index, and histological stage of the gonad were all significantly different in females exposed to 0.5 µg FIP/L compared with those exposed to 5.0 µg FIP/L; however, there were no other significant effects on these measurements in the controls or any of the other treatments in either males and females. Overall, the results do not support a hypothesized adverse outcome pathway linking FIP antagonism of the GABA receptor(s) to reproductive impairment in fish.
γ-氨基丁酸（GABA）及其受体在鱼类神经内分泌调节中发挥着重要作用。环境污染物对 GABA 能系统的破坏可能干扰下丘脑-垂体-性腺轴的正常调节，导致鱼类繁殖受损。本研究采用 21 天的黑头呆鱼（Pimephales promelas）繁殖试验，研究了广谱苯吡唑类杀虫剂氟虫腈（FIP）对鱼类生殖的毒性作用，该杀虫剂作为 GABA 受体门控氯离子通道的非竞争性阻断剂。连续暴露于高达 5μg FIP/L 对大多数测量的终点没有显著影响，包括繁殖力、第二性征、血浆类固醇和卵黄蛋白原浓度、体外类固醇生成以及性腺或脑中的靶向基因表达。与暴露于 5.0μg FIP/L 的对照组相比，暴露于 0.5μg FIP/L 的雌性鱼类的性腺质量、性腺体指数和性腺组织学阶段均有显著差异；然而，在雄性和雌性的对照组或任何其他处理组中，这些测量值均没有其他显著影响。总的来说，结果不支持假设的不良结局途径，即 FIP 拮抗 GABA 受体与鱼类生殖损伤有关。
